It is the broad purpose of this proposal to define clearly the process of ovarian senescence, its precise endocrinologic characteristics, time course, and potential for reversal. These goals will be accomplished by performing a long-term (12 month) longitudinal assessment of the daily urinary excretion of LH, FSH, estrone conjugates and pregnanediol glucuronide in 3 groups of women; two designed to represent the beginning (perimenopausal) and end (postmenopausal) of the menopausal transition, and the third to test the hypothesis that women with premature ovarian failure will match closely the characteristics of at least one of the former two groups. With these data in hand to establish the variability of sex hormone excretion in all 3 groups of women, a second experiment is proposed to test several agents in a prospective randomized, placebo-controlled trial for their effectiveness in reversing the process of ovarian failure. All 3 agents selected: estradiol, GnRH agonist (leuprolide acetate), and corticosteroids (prednisone) have been previously suggested , in uncontrolled reports, to increase the rates of spontaneous ovulation and even pregnancy in women with ovarian failure. Thus, within the three years requested for this award, a comprehensive longitudinal profile of age- appropriate and premature ovarian failure will be achieved, and preliminary information concerning effective therapies for this reproductive disorder will be gained.